Subterranean mammals had to adapt their
biochemical pathways and cellular VDRs
(Vitamin D Receptors) to cope with very
low levels of this hormone:
Vitamin D receptors in a naturally vitamin D-deficient subterranean mammal,
the naked mole rat (Heterocephalus glaber): biochemical characterization.
Sergeev IN, Buffenstein R, Pettifor JM.
Department of Paediatrics, Medical School, University of the Witwatersrand, Johannesburg, South Africa.
1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the hormonally active metabolite of vitamin D3 interacts with its nuclear/cytosolic receptor to induce biological responses in target tissues. Naked mole rats appear to be naturally deficient in vitamin D. The questions arise whether these animals possess the 1,25(OH)2D3 receptor (VDR) and whether they are capable of responding to 1,25(OH)2D3 via receptor-mediated pathways. Various tissues (intestine, kidney, Harderian glands, and skin) were examined for the presence and biochemical characterization (as indicated by saturation, sucrose density gradient, DNA binding, and ligand-competitive analysis) of VDRs. In addition homologous upregulation of VDRs in these tissues and induction of 25-hydroxyvitamin D3-24-hydroxylase (24-OHase) in the kidney was studied as indicators of the VDR-mediated biological responses. Naked mole rats have VDRs in the intestine, kidney, and Harderian gland but not in skin. Biochemical characterization of VDRs and VDR-mediated biological responses in the intestine and kidney correspond to those found in similar target tissues of other mammals. Harderian gland VDR is at a lower concentration yet shows a markedly higher affinity and selectivity to 1,25(OH)2D3 than that of the intestine and kidney. Vitamin D3 supplementation resulted in VDR upregulation in the intestine and kidney and induced renal 24-OHase but had no effects on VDRs in Harderian glands. These data demonstrate that naked mole rats possess VDRs in intestine, kidney, and Harderian glands; these VDRs differ in their biochemical characteristics.
Gen Comp Endocrinol. 1993 Jun;90(3):338-45.
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http://www.cas.vanderbilt.edu/bioimages/animals/mammalia/whetgla30670.jpg
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http://www.alpacasnz.co.nz/images/aobacoverarticles.JPG
VITAMIN D
By Nic Cooper, Southern Alpacas Stud
In the early days of alpacas in New Zealand, the industry saw many cases of carpal valgus (bent or bowed front legs) in alpacas. These ranged from minor to the extreme. The higher concentration appeared to be amongst the darker coloured animals, and it appeared in youngsters, particularly when autumn born, during winter. At Southern Alpacas Stud one of your first cria born, in 1990, developed extreme rickets.
The effect was quickly traced, by researchers, to a vitamin D or phosphorous deficiency, and led to a lot of breeders sprinkling di-calcium phosphate on nuts, and adding other such supplements to nut mixes.
Research in the mid 1990's (ex USA) then indicated that treatment with vitamin D alone would alleviate the clinical signs, and (ex Australia) that di-calcium phosphate was actually bad for your alpacas. But read on for 2005 information ......
Vitamin D (particularly vitamin D3 – chalecalciferol) is necessary to the alpaca to allow it to absorb calcium and phosphorous from the intestinal tract.
Calcium is the most abundant mineral in the body, phosphorous is the second most abundant. These minerals are required for proper bone development. Many enzymes and B vitamins are activated only in the presence of Phosphorous.
Phosphate is the naturally occurring form of the element phosphorus. Phosphate deficiency is what is measured in the bloods, and we treat with a phosphorus compound.
The natural Calcium/Phosphorous ratio in bones and teeth in 2:1, (although 1.5:1 in alpaca is closer to the ideal), and vitamin D is essential for maintaining this balance correctly.
Adequate vitamin D levels also minimise the loss of these two minerals through the kidneys (in excreta).
Vitamin D3 is produced through synthesis in the alpacas skin, from the action of ultraviolet light (sunlight) on cholesterol derivatives. In New Zealand the lower latitudes, and lower altitudes reduce this production, especially in winter, especially in darker pigmented animals, and especially in animals with denser fleeces.
Vitamin D also comes from consumption of sun cured dried foods, such as hay (which has vitamin D2). A lush grass diet in NZ also therefore limits the production of vitamin D in the alpaca.
In addition, on lush pastures, high concentrations of carotenes can tie up vitamin D making less available to the body.
...
updated November 2005.
complete article: http://www.alpacasnz.co.nz/articles-vitamind.htm (http://www.alpacasnz.co.nz/articles-vitamind.htm)
Here I learned that hay is actually 'medicated grass' because of vitamin D2 production through sunlight exposure!
This would imply that one could create synthetic chemicals that could bind to the same receptors as vitamin D3 does itself, and either enhance or block the effect of the vitamin in that way.
It ofcourse also leads to the question as to what is happening downstream of the VDR's?
Just idle curiosity.
Right.
Vitamin D is a hormone of the steroid family, with its specific receptors on certain cells and seems to control the expression of more than 200 genes. Did you by any chance read a recent review on vitamin D by Michael Holick? It's full-text free in a prestigious journal like JCI: in my experience big medical 'news' have been published here first...
Plenty of references and many of them free full-text!
http://www.jci.org/cgi/content/full/116/8/2062
Resurrection of vitamin D deficiency and rickets.
Holick MF.
Department of Medicine, Section of Endocrinology, Nutrition, and Diabetes, and Vitamin D, Skin and Bone Research Laboratory, Boston University Medical Center, Boston, Massachusetts 02118, USA. mfholick@bu.edu
The epidemic scourge of rickets in the 19th century was caused by vitamin D deficiency due to inadequate sun exposure and resulted in growth retardation, muscle weakness, skeletal deformities, hypocalcemia, tetany, and seizures. The encouragement of sensible sun exposure and the fortification of milk with vitamin D resulted in almost complete eradication of the disease. Vitamin D (where D represents D2 or D3) is biologically inert and metabolized in the liver to 25-hydroxyvitamin D [25(OH)D], the major circulating form of vitamin D that is used to determine vitamin D status. 25(OH)D is activated in the kidneys to 1,25-dihydroxyvitamin D [1,25(OH)2D], which regulates calcium, phosphorus, and bone metabolism. Vitamin D deficiency has again become an epidemic in children, and rickets has become a global health issue. In addition to vitamin D deficiency, calcium deficiency and acquired and inherited disorders of vitamin D, calcium, and phosphorus metabolism cause rickets. This review summarizes the role of vitamin D in the prevention of rickets and its importance in the overall health and welfare of infants and children.
J Clin Invest. 2006 Aug;116(8):2062-72.